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Biological Networks Analysis Introduction and Dijkstra’s algorithm

Biological Networks Analysis Introduction and Dijkstra’s algorithm. Genome 559: Introduction to Statistical and Computational Genomics Elhanan Borenstein. A quick review. The clustering problem: partition genes into distinct sets with high homogeneity and high separation

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Biological Networks Analysis Introduction and Dijkstra’s algorithm

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  1. Biological Networks AnalysisIntroduction and Dijkstra’s algorithm Genome 559: Introduction to Statistical and Computational Genomics Elhanan Borenstein

  2. A quick review • The clustering problem: • partition genes into distinct sets with high homogeneity and high separation • Hierarchical clustering algorithm: • Assign each object to a separate cluster. • Regroup the pair of clusters with shortest distance. • Repeat 2 until there is a single cluster. • Many possible distance metrics • K-mean clustering algorithm: • Arbitrarily select k initial centers • Assign each element to the closest center • Voronoi diagram • Re-calculate centers (i.e., means) • Repeat 2 and 3 until termination condition reached

  3. Biological networks What is a network? What networks are used in biology? Why do we need networks (and network theory)? How do we find the shortest path between two nodes?

  4. Networks vs. Graphs

  5. What is a network? • A map of interactions or relationships • A collection of nodes and links (edges)

  6. What is a network? • A map of interactions or relationships • A collection of nodes and links (edges)

  7. Types of networks • Edges: • Directed/undirected • Weighted/non-weighted • Simple-edges/Hyperedges • Special topologies: • Directed Acyclic Graphs (DAG) • Trees • Bipartite networks

  8. Transcriptional regulatory networks • Reflect the cell’s genetic regulatory circuitry • Nodes: transcription factors and genes; • Edges: from TF to the genes it regulates • Directed; weighted?; “almost” bipartite • Derived through: • Chromatin IP • Microarrays • Computationally

  9. Metabolic networks • Reflect the set of biochemical reactions in a cell • Nodes: metabolites • Edges: biochemical reactions • Directed; weighted?; hyperedges? • Derived through: • Knowledge of biochemistry • Metabolic flux measurements • Homology? S. Cerevisiae 1062 metabolites 1149 reactions

  10. Protein-protein interaction (PPI) networks • Reflect the cell’s molecular interactions and signaling pathways (interactome) • Nodes: proteins • Edges: interactions(?) • Undirected • High-throughput experiments: • Protein Complex-IP (Co-IP) • Yeast two-hybrid • Computationally S. Cerevisiae 4389 proteins 14319 interactions

  11. Other networks in biology/medicine

  12. Non-biological networks • Computer related networks: • WWW; Internet backbone • Communications and IP • Social networks: • Friendship (facebook; clubs) • Citations / information flow • Co-authorships (papers) • Co-occurrence (movies; Jazz) • Transportation: • Highway systems; Airline routes • Electronic/Logic circuits • Many many more…

  13. Why networks? • Networks as models • Networks as tools • Simple, visual representationof complex systems Focus on organization(rather than on components) • Algorithm development • Problem representation(more common than you think) • Discovery(topology affects function) • Predictive models • Diffusion models(dynamics)

  14. The Seven Bridges of Königsberg • Published by Leonhard Euler, 1736 • Considered the first paper in graph theory Leonhard Euler1707 –1783

  15. The shortest path problem • Find the minimal number of “links” connecting node A to node B in an undirected network • How many friends between you and someone on FB(6 degrees of separation) • Erdös number, Kevin Bacon number • How far apart are 2 genes in an interaction network • What is the shortest (and likely) infection path • Find the shortest (cheapest) path between two nodes in a weighted directed graph • GPS; Google map

  16. Dijkstra’s Algorithm "Computer Science is no more about computers than astronomy is about telescopes." EdsgerWybeDijkstra1930 –2002

  17. Dijkstra’s algorithm • Solves the single-source shortest path problem: • Find the shortest path from a single source to ALL nodes in the network • Works on both directed and undirectednetworks • Works on both weighted and non-weighted networks • Approach: • Iterative • Maintain shortest path to each intermediate node • Greedy algorithm • … but still guaranteed to provide optimal solution !!!

  18. Dijkstra’salgorithm • Initialize: • Assign a distance value, D, to each node. Set D to zero for start node and to infinity for all others. • Mark all nodes as unvisited. • Set startnode as current node. • For each of the current node’s unvisited neighbors: • Calculate tentative distance, Dt, through current node. • If Dt smaller than D (previously recorded distance): D Dt • Mark current node as visited (note: shortest dist. found). • Set the unvisited node with the smallest distance as the next "current node" and continue from step 2. • Once all nodes are marked as visited, finish.

  19. Dijkstra’s algorithm • A simple synthetic network 2 5 B D 9 1 4 9 F A 3 7 3 C E 12 2 • Initialize: • Assign a distance value, D, to each node. Set D to zero for start node and to infinity for all others. • Mark all nodes as unvisited. • Set startnode as current node. • For each of the current node’s unvisited neighbors: • Calculate tentative distance, Dt, through current node. • If Dt smaller than D (previously recorded distance): D Dt • Mark current node as visited (note: shortest dist. found). • Set the unvisited node with the smallest distance as the next "current node" and continue from step 2. • Once all nodes are marked as visited, finish.

  20. Dijkstra’s algorithm • Initialization • Mark A (start) as current node 2 D: ∞ D: ∞ 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞ D: ∞ 2

  21. Dijkstra’s algorithm • Check unvisited neighbors of A 2 0+9 vs. ∞ D: ∞ D: ∞ 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞ D: ∞ 2 0+3 vs. ∞

  22. Dijkstra’s algorithm • Update D • Record path 2 D: ∞ D: ∞,9 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞ 2

  23. Dijkstra’s algorithm • Mark A as visited … 2 D: ∞ D: ∞,9 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞ 2

  24. Dijkstra’s algorithm • Mark C as current (unvisited node with smallest D) 2 D: ∞ D: ∞,9 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞ 2

  25. Dijkstra’s algorithm • Check unvisited neighbors of C 2 3+3 vs. ∞ 3+4 vs. 9 D: ∞ D: ∞,9 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞ 3+2 vs. ∞ 2

  26. Dijkstra’s algorithm • Update distance • Record path 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞,5 2

  27. Dijkstra’s algorithm • Mark C as visited • Note: Distance to C is final!! 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞,5 2

  28. Dijkstra’s algorithm • Mark E as current node • Check unvisited neighbors of E 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞ 3 C E 12 D: ∞,3 D: ∞,5 2

  29. Dijkstra’s algorithm • Update D • Record path 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: 0 D: ∞,17 3 C E 12 D: ∞,3 D: ∞,5 2

  30. Dijkstra’s algorithm • Mark E as visited 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17 3 C E 12 D: ∞,3 D: ∞,5 2

  31. Dijkstra’s algorithm • Mark D as current node • Check unvisited neighbors of D 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17 3 C E 12 D: ∞,3 D: ∞,5 2

  32. Dijkstra’s algorithm • Update D • Record path (note: path has changed) 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  33. Dijkstra’s algorithm • Mark D as visited 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  34. Dijkstra’s algorithm • Mark B as current node • Check neighbors 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  35. Dijkstra’s algorithm • No updates.. • Mark B as visited 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  36. Dijkstra’s algorithm • Mark F as current 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  37. Dijkstra’s algorithm • Mark F as visited 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2

  38. We are done! • We now have: • Shortest path from A to each node (both length and path) • Minimum spanning tree 2 D: ∞,6 D: ∞,9,7 5 B D 9 1 4 9 F A 3 7 D: 0 D: ∞,17,11 3 C E 12 D: ∞,3 D: ∞,5 2 • Will we always get a tree? • Can you prove it?

  39. Computational Representationof Networks A B C D Object Oriented • List of edges:(ordered) pairs of nodes[ (A,C) , (C,B) , (D,B) , (D,C) ] Connectivity Matrix Name:Dngr: Name:Cngr: Name:Angr: Name:Bngr: p1 p1 p1 p2 • Which is the most useful representation?

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